Validation of the integrated 40-gene expression profile (i40-GEP) which provides prognostic and adjuvant radiation benefit for high-risk cutaneous squamous cell carcinoma.

BACKGROUND

Risk assessment in high-risk cutaneous squamous cell carcinoma uses several clinicopathologic staging system tools, yet under- and overtreatment often occur. Integration of tumor biology as an independent predictor via gene expression profile (GEP) may improve risk stratification and tailor adjuvant care.

OBJECTIVE

Integrate clinicopathologic risk factors with 40-GEP testing to refine risk stratification.

METHODS

Integrated 40-GEP (i40-GEP) combines optimized nested predictive models and 5 clinicopathologic features (immunosuppression, location, differentiation, tumor diameter, and perineural invasion) with the validated 40-GEP, and reports results: Class 1A (low risk), Class 1B (moderate risk), Class 2A (high risk), and Class 2B (highest risk).

RESULTS

i40-GEP significantly stratifies metastatic and local recurrence risk (P < .0001) in a validation cohort (n = 572), with >95% negative predictive value for Class 1A across National Comprehensive Cancer Network subsets. The i40-GEP identified 12.9% of patients as Class 2B, with the lowest 3-year metastasis-free survival (66.2%) and a demonstrated benefit from adjuvant radiation treatment (ART). Multivariable analysis showed i40-GEP results significantly predict metastatic and local recurrence risk more than individual clinicopathologic factors.

LIMITATIONS: Retrospective study.

CONCLUSIONS

i40-GEP accurately stratifies metastatic and local recurrence risk in patients with high-risk cutaneous squamous cell carcinoma, leading to improved clinical decision-making. Class 2B i40-GEP identifies patients most likely to benefit from ART.